This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this research is to use peptides, polymers or liposomes to deliver their contents into the cytoplasm of cells, to characterize the mechanism of delivery and to exploit the low pH environment of the endosome or lysosome to catalyze delivery of polymer/liposomal contents into cytoplasm. Another goal of this research is to develop gene and drug approaches to treat cancer. A third goal of our research is to develop improved adjuvants to use in human vaccines. One approach is to synthesize novel peptide lipids or peptide polymers that can undergo a low pH induced conformational change that results in the exposure of hydrophobic sequences that initiate membrane fusion. The peptide would be attached to the surface of the polymer or liposome in this application. A second approach is to synthesize prodrugs that can undergo either a pH dependent or enzymatic modification which permits their efflux from the lysosomal compartment. In either of these applications chemical and physical approaches are being used to design more efficient drug delivery systems and to determine the limitations to their use. We are also developing peptides that can attach to cellular molecular motors to direct the drug or gene to particular locations such as the nucleus in the cell.